Researchers isolate protein that delivers brain benefits of exercise

A protein produced during endurance exercise has been isolated and given to non-exercising mice, where it switched on genes that promote brain health and encouraged the growth of new nerves and synapses involved in learning and memory. The breakthrough was reported by scientists from Dana-Farber Cancer Institute and Harvard Medical School and is detailed in the journal Cell Metabolism.

The new work goes a long way to explaining how endurance exercise can improve cognitive function, particularly in older people. The researchers think it could eventually lead to improved therapies for cognitive decline in older people and slow the toll of neurodegenerative diseases such Alzheimer’s and Parkinson’s.

“What is exciting is that a natural substance can be given in the bloodstream that can mimic some of the effects of endurance exercise on the brain,” said researcher Bruce Spiegelman, of Dana-Farber.

Spiegelman’s research team previously reported that the protein, called FNDC5, is produced by muscular exertion and is released into the bloodstream as a variant called irisin. In the new research, endurance exercise increased the activity of a metabolic regulatory molecule, PGC-1á, in muscles, which spurred a rise in FNDC5 protein. The increase of FNDC5 in turn boosted the expression of a brain-health protein, BDNF (brain-derived neurotrophic protein) in the hippocampus, a part of the brain involved in learning and memory.

How exercise raises BDNF activity in the brain wasn’t previously understood. The new findings linking exercise, PGC-1á, FNDC5, and BDNF provide a molecular pathway for the effect.

Having shown that FNDC5 is a link between exercise and increased BDNF in the brain, the scientists asked whether artificially increasing FNDC5 in the absence of exercise would have the same effect. To investigate, they used a harmless virus to deliver the protein to mice through the bloodstream, in hopes the FNDC5 could reach the brain and raise BDNF activity. Seven days later, they examined the mouse brains and observed a significant increase in BDNF in the hippocampus.

“Perhaps the most exciting result overall is that peripheral delivery of FNDC5 with adenoviral vectors is sufficient to induce central expression of BDNF and other genes with potential neuroprotective functions or those involved in learning and memory,” Spiegelman said. However, he cautions that more research is required before a treatment for humans will become available as a more stable form of the protein is required.